Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds

Journal Article · Sat Dec 01 00:00:00 EST 2007 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2007.07.013· OSTI ID:21077861

Gracia, Tannia ^[1]; Hilscherova, Klara ^[2]; Jones, Paul D ^[1]; Newsted, John L ^[3]; Higley, Eric B ^[1]; Zhang, Xiaowei ^[1]; Hecker, Markus ^[1]; Murphy, Margaret B; Yu, Richard M.K.; Lam, Paul K.S.; Wu, Rudolf S.S. ^[4]; Giesy, John P ^[1]

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1. Department of Zoology, National Food Safety and Toxicology Center, Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States)
2. Research Centre for Environmental Chemistry and Ecotoxicology, Masaryk University, Kamenice 3, 625 00 Brno (Czech Republic)
3. ENTRIX Inc., 2295 Okemos Rd., East Lansing, MI 48864 (United States)
4. City University of Hong Kong, Tat Chee Ave, Kowloon, Hong Kong (China)

The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3{beta}HSD2, CYP11{beta}1, CYP11{beta}2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11{beta}2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11{beta}2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The {beta}-blocker salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different.

• OSTI ID: 21077861
• Journal Information: Toxicology and Applied Pharmacology, Vol. 225, Issue 2; Other Information: DOI: 10.1016/j.taap.2007.07.013; PII: S0041-008X(07)00331-6; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BINARY MIXTURES
BIOASSAY
DOSES
ERYTHROMYCIN
ESTRADIOL
GENES
POLYMERASE CHAIN REACTION
PROGESTERONE
TESTOSTERONE